Adaptations of proteins towards an increased thermostability can be observed in nature in environments such as the marine hydrothermal vents. The principles behind an increased thermostability can then be used in the biotech industry in order to design proteins with high stability. The demand for an increased stability has to be balanced by the dynamic required for maintaining catalytic activity of the enzyme. The (hyper-)thermophilic proteins are composed of the common 20 natural amino acids. Optimization of interactions between the amino acids in the peptide chain is hence a key feature for an increased stability. By comparing structures of (hyper-)thermophilic proteins with the mesophilic counterparts it is demonstrated that an increased stability is achieved through a combination of a variety of stabilizing interactions. The thermostabilizing interactions include improved packing of the protein structure and optimization of hydrophobic and electrostatic interactions. Furthermore the structure could be stabilized by a covalent crosslink in terms of a disulfide bond. In this paper the different interactions are presented and examples are given on how the interactions can be optimized to increase the thermostability of specific proteins. Finally, lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase serve as two illustrative examples of how the different interactions can be used in combination in order to improve the thermostability.